Immunization with recombinant Nogo-66 receptor (NgR) promotes axonal regeneration and recovery of function after spinal cord injury in rats.
Nogo-66 receptor (NgR), a common receptor for the three known myelin-associated inhibitors, i.e., Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), plays a key role in the failure of axonal regeneration in the adult mammalian central nervous system (CNS). Here we report a novel vaccine approach that stimulates the production of anti-NgR antibody to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). We showed that adult rats immunized with recombinant NgR produced high titers of the anti-NgR antibody and that antisera obtained from the immunized rats promoted neurite outgrowth of rat cerebellar neurons on the inhibitory MAG substrate in vitro. In a spinal cord dorsal hemisection model, NgR immunization promoted regeneration of lesioned corticospinal tract (CST) axons, anterogradely labeled with biotin dextran amine (BDA), beyond the lesion site. In a contusive SCI model, NgR immunization markedly reduced the total lesion volume and improved Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and grid walking performance. Thus, the NgR vaccine approach may represent a promising repair strategy to promote structural and functional recovery following SCI.
Yu
Panpan
P
Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Huang
Lidong
L
Zou
Jian
J
Yu
Zhihua
Z
Wang
Yanxia
Y
Wang
Xiaofei
X
Xu
Liang
L
Liu
Xinqiu
X
Xu
Xiao-Ming
XM
Lu
Pei-Hua
PH
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000097:blood; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D009185:Myelin Proteins / Q000276:immunology*; D009416:Nerve Regeneration; D016501:Neurites / Q000502:physiology; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000276:immunology*; D020127:Recovery of Function; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
D000906:Antibodies; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; D014614:Vaccines, Synthetic